P730: EVOLUTION OF IPSS-M RISK CATEGORIES IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES FROM DIAGNOSIS TO HYPOMETHYLATING AGENT FAILURE
Authors: Kelly Chien, Samuel Urrutia, Ziyi LI, Rashmi Kanagal-Shamanna, Emmanuel Almanza, Tareq Abuasab, Georgina Gener, Alex Bataller, Alexandre Bazinet, Guillermo Montalban-Bravo, Nicholas Short, Elias Jabbour, Tapan Kadia, Farhad Ravandi, Gautam Borthakur, Danielle Hammond, Mahesh Swaminathan, Koji Sasaki, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: HemaSphere (2023)

Background: Hypomethylating agents (HMA) improve cytopenia and delay progression of disease in patients (pts) with myelodysplastic syndromes (MDS). Most eventually lose response to these agents with poor survival outcomes afterward, posing significant treatment challenges after HMA failure (HMA-F). The Molecular International Prognostic Scoring System (IPSS-M) was recently developed to risk stratify pts with the addition of mutational data. However, the evolution of this prognostication tool from diagnosis to HMA-F remains unknown. Aims: We assess the clinical characteristics and outcomes of pts with MDS by their change in IPSS-M risk categories from diagnosis to HMA-F. Methods: We evaluated all pts with MDS seen at a tertiary cancer center from July 2017 to July 2021 and identified those who were previously untreated and later developed HMA-F. Patient characteristics, laboratory values, and bone marrow data, including cytogenetics and next generation sequencing (NGS) with an 81-gene panel, were assessed at both diagnosis and HMA-F. IPSS-M scores were calculated at both time points, and pts were categorized by their change in risk stratification. Results: A total of 101 pts were included and divided into 3 cohorts: 39 upstaged, 25 downstaged, and 37 with the same IPSS-M risk at the time of HMA-F (Figure). There were no differences in age, gender, or incidence of therapy-related MDS between the 3 cohorts. Regarding baseline laboratory values, pts who later upstaged had higher white blood cell counts (p=0.035), absolute neutrophil counts (p=0.031), and hemoglobin (p<0.001) than those who downstaged or remained the same. Though there were no differences in cytogenetic risk groups between the cohorts (p=0.140), pts who upstaged (19%) were less likely to have complex karyotype, than those who downstaged (48%) or remained the same (50%, p=0.011). On NGS, those who upstaged (16%) were more likely to have no mutations than those who downstaged (4%) or had no change (0%, p=0.024). Furthermore, no differences in number of HMA cycles received, HMA monotherapy vs combination therapy, response to HMA, and type of progression at HMA-F (blast increase or worsening cytopenia) were observed, but pts who had a change in IPSS-M risk were more likely to have secondary HMA-F after at least 6 cycles of therapy than those whose IPSS-M remained the same (67% vs 43%, p=0.019). Regarding outcomes, pts who upstaged by IPSS-M had superior median overall survival (mOS) from diagnosis and time to HMA-F than those who downstaged or remained the same (mOS from diagnosis: 36.2 vs 21.3 vs 22.5 months (mo) respectively, p=0.086; time to HMA-F: 20.7 vs 12.4 vs 11.4 mo respectively, p=0.115). This difference was also observed when comparing the mOS from HMA-F of upstaged pts (16.70 mo) with those who downstaged (7.23 mo) or remained the same (9.90 mo, p=0.100) and more pronounced when only comparing upstaged vs downstaged pts (p=0.041). There were no differences in pts who underwent allogeneic stem cell transplantation or transformation to AML between the groups. Summary/Conclusion: Sequential changes in IPSS-M show that pts who upstage at the time of HMA-F have improved survival outcomes from both diagnosis and HMA-F compared to those who downstage or have no change in IPSS-M risk categorization. This implies that IPSS-M at baseline has more prognostic value than after HMA therapy. Further validation of IPSS-M or the development of a risk stratification system at the time of HMA-F is warranted.Keywords: Myelodysplastic syndrome, MDS, Prognostic groups, Hypomethylating agents